Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines

Ohkawa, Kiyoshi; Hibi, Nozomu; Tsutsumi, Yutaka

doi:10.1007/bf00199119

Cited by 15 publications

(5 citation statements)

References 18 publications

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“…The human yolk sac tumor JOG-9 used in this study was established by SC inoculation of fresh tumor tissues from a 14-year-old female patient diagnosed as pure ovarian yolk sac tumor at surgery into nude mice in our laboratory [11]. The donor patient had not received chemotherapy.…”

Section: Methodsmentioning

confidence: 99%

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Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human ?-fetoprotein conjugated with mitomycin C via human serum albumin

Ohkawa¹,

Tsutsumi²,

Hibi³

et al. 1986

Cancer Immunol Immunother

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The anticancer drug mitomycin C (MMC) was conjugated with an affinity-purified horse antibody to human alpha-fetoprotein (aAFP) with human serum albumin (HSA) as the intermediate drug carrier. The conjugate (aAFP:HSA:MMC molar ratio, 1:1:30) retained full antibody binding activity as determined by a competitive binding radioimmunoassay. In a cytotoxicity test in which the AFP-producing human yolk sac tumor TG-1 cells were preincubated with test materials for 2 h followed by an additional 48-h culture in fresh medium, the conjugate was 20-fold more cytotoxic than free MMC at an equivalent MMC concentration of 100 ng/ml. The in vivo antitumor effect of the conjugate was tested against the human yolk sac tumor JOG-9 growing in athymic nude mice. When the tumor-bearing mice were treated with a total of 6 injections given on 2 consecutive days and then every other day starting 8 days after SC tumor inoculation [2 (equivalent MMC) microgram/head per injection], the conjugate retarded tumor growth more effectively than free MMC and normal horse immunoglobulin conjugate.

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Section: Methodsmentioning

confidence: 99%

“…JOG-9 and TG-1 were established in our laboratories a few years ago and are AFPproducing [11]. Localization of AFP at JOG-9 implanted and grown in nude mice has previously been demonstrated in our laboratory [11].…”

Section: Introductionmentioning

confidence: 97%

Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human ?-fetoprotein conjugated with mitomycin C via human serum albumin

Ohkawa¹,

Tsutsumi²,

Hibi³

et al. 1986

Cancer Immunol Immunother

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“…The human yolk sac tumour (JOG-9) used in this study was established by s.c. inoculation of a 'pure' ovarian yolk sac tumour obtained from a 14-year old female patient (Ohkawa et al, 1986a). The donor had not received chemotherapy.…”

Section: Tumourmentioning

confidence: 99%

The effects of co-administration of selenium and cis-platin (CDDP) on CDDP-induced toxicity and antitumour activity

Ohkawa

Tsutsumi²,

Dohzono³

et al. 1988

Br J Cancer

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Summary The therapeutic antitumour activity and host toxicity of cis-platin (CDDP), which was administered with selenium (sodium selenite) was studied on the growth of a human yolk sac tumour grown in nude mice. Treatment consisted of CDDP single agent chemotherapy (3 weeks) or preliminary PVB combination chemotherapy (CDDP+vinblastine +bleomycin, 2 weeks). Selenium was co-administered from day 1 to 5 with each therapeutic regimen. The administration of CDDP alone caused significant reduction in tumour burden but at higher doses there was significant host toxicity. The co-administration of selenium together with CDDP (CDDP: selenium, molar ratio=3.5:1) did not affect the anti-tumour activity of CDDP but it did cause a decrease of parameters of host toxicity including lethality, increasing the 50% lethal dose (LD50) from 9.3mg kg-1 to 17.5mg kg -1. The parameters of host toxicity which were altered by selenium co-administration were nephrotoxicity, myeloid suppression and weight loss. Our study suggested that selenium coadministration allows higher doses of CDDP with reduction of apparent toxicity, resulting in a higher therapeutic index and possibly indicating a potential increase in the utilization of CDDP in clinical cancer chemotherapy.

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“…These immunoconjugates have shown efficacy against tumor cells in vitro and, less frequently, against tumor in vivo in animals [27, 30, 38, 43, 50, 54-57, 59, 61]. In addition, small drugs currently used for the treatment of neoplasia have been conjugated to MCA or polyclonal antisera and have shown some efficacy against animal tumors in vivo [1,13,40,41,46,47,51]. A large number of these animal tumor models have been human xenografts in congenitally athymic nude mice.…”

Section: Introductionmentioning

confidence: 98%

The antileukemic efficacy of an immunotoxin composed of a monoclonal anti-Thy-1 antibody disulfide linked to the ribosome-inactivating protein gelonin

Scott

Goldmacher

Lambert

et al. 1987

Cancer Immunol Immunother

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We prepared an immunoconjugate consisting of a monoclonal antibody recognizing the Thy-1 antigen and the ribosome-inactivating protein gelonin linked by a disulfide bond. This immunotoxin preparation was judged to contain less than 5% free antibody or gelonin. It was highly toxic in vitro in an antigen-specific fashion to the Thy-1 expressing RADA leukemia of A/J mice. The IC50 of this preparation on RADA in vitro was 10(-12) M, while the IC50 on the Thy-1 negative S1509a fibrosarcoma of A/J mice was 10(-7) M. The toxicity of this immunoconjugate was also measured in a direct proliferation and it was found that a 4-h exposure and a 24-h exposure of RADA cells to a 1 nM concentration of immunotoxin killed 90% and 99.9% of cells, respectively. Furthermore, efficacy in vitro was not due to the intrinsic susceptibility of RADA cells to tis type of immunotoxin, as one prepared with gelonin and an antibody recognizing the TLa determinant on this leukemia had no efficacy in vitro. Clearance of the anti-Thy-1-gelonin immunoconjugate from the circulation of A/J mice after i.v. injection was rapid, especially during the first 8 h after injection, possibly because of binding to Thy-1 expressing tissue. Delivery of immunoconjugate to ascitic tumor in vivo was substantially better if the immunoconjugate was given by i.p. injection, rather than by the i.v. route. When given either i.v. or i.p. at the time of i.p. tumor inoculation in vivo, the anti-Thy-1-gelonin immunotoxin showed potency in an antigen-specific fashion; while this immunoconjugate prolonged survival and frequently cured RADA-inoculated mice, neither anti-Thy-1 antibody, gelonin, a combination of the two, nor immunotoxin of irrelevant specificity had any significant effect on survival. Anti-Thy-1-gelonin also had no effect on survival of A/J mice inoculated i.p. with S1509a. Furthermore, it was determined that a single i.p. dose of anti-Thy-1-gelonin killed 90% to 99% cells in vivo, and that the immunoconjugate was about as effective in this model as either adriamycin or cytoxan.

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Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines

Cited by 15 publications

References 18 publications

Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human ?-fetoprotein conjugated with mitomycin C via human serum albumin

Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human ?-fetoprotein conjugated with mitomycin C via human serum albumin

The effects of co-administration of selenium and cis-platin (CDDP) on CDDP-induced toxicity and antitumour activity

The antileukemic efficacy of an immunotoxin composed of a monoclonal anti-Thy-1 antibody disulfide linked to the ribosome-inactivating protein gelonin

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